Recent evidence suggests that imbalance in the proteinase-antiproteinase defense system may be a factor in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease that occurs in neonates as a sequella of prolonged 02 and ventilator therapy for respiratory distress. The major proteinase inhibitor in the alveolar regions of the lung, Alpha1-proteinase inhibitor (Alpha1-PI), is inactivated in lungs of infants treated with inspired oxygen concentrations (FIO2) greater than 0.6 for 6 or more days. Furthermore, alveolar macrophages and polymorphonuclear leukocytes containing proteolytic enzymes, i.e. elastase, are found in increased numbers in lung secretions of infants with respiratory distress treated for several days with a high FIO2, and a 10-20 fold increase in elastase activity has been observed in these infants. Uninhibited proteolytic enzymes could initiate or exacerbate pathologic changes associated with BPD such as damage to ciliated cells, focal emphysema, and squamous metaplasia of bronchial/bronchiolar epithelium. These enzymes could also degrade structural proteins in the lung such as elastin, collagen, and proteoglycans. Because elastin plays a major role in the development of true alveoli from the immature saccules present at birth, proteolysis of elastin could alter the course of neonatal lung development. Our objectives are to quantitate, by amino acid analysis, the degradation products of elastin (desmosines) contained in the urine and lung secretions and to determine whether there is a correlation between 02/ventilatory therapy and degradation of lung elastin. Next we will attempt to correlate, in individual infants, the antiproteinase status of lung secretions (determined by cytological examination, proteinase inhibitory capacity and concentration of free elastase) with degradation of lung elastin. Data on antiproteinase status and degradation of lung elastin will then be correlated with appearance of clinical and pathological evidence of chronic lung disease. In addition, we plan to investigate in the neonatal rat lung the influence of chronic hyperoxia, a major etiologic factor BPD, on lung maturation and lung elastin content. We anticipate that these studies will help to clarify the pathogenetic mechanisms of BPD and facilitate early recognition of infants at risk for developing chronic lung disease.